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Immunological predictors of nodal response in breast cancer patients undergoing neoadjuvant therapy Maria Luisa Gasparri1, Ilary Ruscito2, Filippo Bellati2, Fabio Corsi3, Rosa Di Micco4, Oreste D. Gentilini4, Thorsten Kuehn5, Andrea Papadia1, Donatella Caserta2, Lorenzo Rossi6, Arianna Calcinotto7 1 Department of Gynecology and Obstetrics, Ente Ospedaliero Cantonale, Ospedale Regionale di Lugano, Lugano, Switzerland 2 Department of Medical and Surgical Science and Translational Medicine, Sapienza University of Rome, Azienda Ospedaliera Sant’Andrea, Rome, Italy 3 Breast Unit, Department of Surgery, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy; Department of Biomedical and Clinical Sciences "Luigi Sacco", Università di Milano, Milan, Italy 4 Breast Surgery Unit, San Raffaele University Hospital, Milan, Italy 5 Interdisciplinary Breast Center, Department of Gynecology and Obstetrics, Klinikum Esslingen, Esslingen, Germany 6 Oncology Institute of Southern Switzerland, Bellinzona, Switzerland 7 Cancer Immunotherapy lab, IOR Institute of Oncology Research, Bellinzona, Switzerland Background: Almost 20% of breast cancer patients present at diagnosis with clinically positive nodes. Most of these patients undergo neoadjuvant therapy in order to de-escalate the axillary surgery in case of response (sentinel lymph node biopsy, targeted axillary dissection or targeted axillary dissection, instead of an axillary lymphadenectomy). The conversion from positive to negative nodes after neoadjuvant therpy is expected in approximately the 60% of the cases, depending by tumor subtypes. Several models have been proposed with the goal of identifying predictors of nodal response prior to neoadjuvant treatment. The immune system plays a pivotal role in cancer invasion and progression. Its role in treatment response is currently under investigation in several settings. Primary endpoint: to identify a preoperative immune profiling of breast cancer patients with nodal involvement at diagnosis and to correlate the immune changes after neoadjuvant therapy with the nodal response (macrometastases, micrometastasis, isolated tumor cells, complete response). Trial design: It is an international prospective cohort study including breast cancer patients undergoing standard neoadjuvant therapy, who present initially with biopsy-proven axillary lymph node metastasis. Ten immune markers will be analyzed using immunohistochemistry and tissue microarray in primary tumor and nodal tissue samples (tumor associated neutrophils, CD4 lymphocytes, CD8 lymphocytes, T regulatory cells, Macrophages, Follicular dendritic cells(DC), plasmocytoid DC, interdigitant DC, mature DC, Lysosomal associated membrane protein 3). The tissue analysis will be performed on the biopsy collected at diagnosis (prior to neoadjuvant therapy) and during the axillary surgery (after neoadjuvant therapy). Target accrual/sample size: 210 patients Statistical analysis: To compare the distribution of immune cells according to the state of lymph node metastasis, Student’s t test will be performed. Pearson’s chi-square test will be used to evaluate the correlation between immune profile and nodal response, based on clinic-pathological features. Odds ratios (ORs) and 95% confidence intervals (CIs) will be calculated using logistic regression analysis. Multivariable analysis will be performed using the multivariable logistic regression model. Logistic regression models will be used to identify the clinical, pathologic and immunological variables associated with the nodal response. P-values less than 0.05 will be considered significant. Analyses will be performed using Microsoft IBM SPSS® version 20.0 for Mac. Current status: Recruitment has not started yet. Contact information: marialuisa.gasparri@eoc.ch Citation Format: Maria Luisa Gasparri, Ilary Ruscito, Filippo Bellati, Fabio Corsi, Rosa Di Micco, Oreste Davide Gentilini, Thorsten Kuehn, Andrea Papadia, Donatella Caserta, Lorenzo Rossi, Arianna Calcinotto. Immunological predictors of nodal response in breast cancer patients undergoing neoadjuvant therapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT3-12-01.

Background US-indeterminate adnexal lesions remain an important indication for gynecologic surgery. MRI can serve as a problem-solving tool through the use of the Ovarian-Adnexal Imaging Reporting and Data System (O-RADS) MRI lexicon, which is based on the ADNEX MR scoring system. Purpose To perform a systematic review and meta-analysis of the diagnostic performance of pelvic MRI interpreted using the ADNEX or O-RADS MRI stratification systems to characterize US-indeterminate adnexal lesions and of the category-wise malignancy rates. Materials and Methods A systematic literature search from May 2013 (publication of the ADNEX MR score) to September 2022 was performed. Studies reporting the use of pelvic MRI interpreted with the ADNEX or O-RADS MRI systems to characterize US-indeterminate adnexal lesions, with pathologic examination and/or follow-up as the reference standard, were included. Summary estimates of diagnostic performance were obtained with the bivariate random-effects model, while category-wise summary malignancy rates of O-RADS MRI 2, 3, 4, and 5 lesions were obtained with a random-effects model. Effects of covariates on heterogeneity and diagnostic performance were investigated through meta-regression. Results Thirteen study parts from 12 studies (3731 women, 4520 adnexal lesions) met the inclusion criteria. Diagnostic performance meta-analysis for 4012 lesions found a 92% summary sensitivity (95% CI: 88, 95) and a 91% summary specificity (95% CI: 89, 93). The meta-analysis of malignancy rates for 3641 lesions showed summary malignancy rates of 0.1% (95% CI: 0, 1) among O-RADS MRI 2 lesions, 6% (95% CI: 3, 9) among O-RADS MRI 3 lesions, 60% (95% CI: 52, 67) among O-RADS MRI 4 lesions, and 96% (95% CI: 92, 99) among O-RADS MRI 5 lesions. Conclusion Pelvic MRI interpreted with the Ovarian-Adnexal Reporting and Data System (O-RADS) MRI lexicon had high diagnostic performance for the characterization of US-indeterminate adnexal lesions. Summary estimates of malignancy rates in the O-RADS MRI 4 and O-RADS MRI 5 categories were higher than predicted ones. © RSNA, 2022

Introduction and hypothesis Few studies in literature have assessed the long-term durability and mesh-related complications of mid-urethral slings (MUSs). The aim of this study is to assess the efficacy and safety of retro-pubic tension-free vaginal tape (TVT) 20 years after implantation for the treatment of female stress urinary incontinence (SUI). Methods A prospective observational study was conducted in two urogynaecologic units in two countries. All the patients involved were consecutive women with urodynamically proven pure SUI treated by TVT. The patients underwent preoperative clinical and urodynamic evaluations. Subjective outcomes, objective outcomes and adverse events were recorded during the follow-up period. Results Fifty-two patients underwent a TVT surgical procedure. Twenty years after surgery, 32 out of 36 patients (88.8%) declared themselves cured (p = 0.98). Similarly, 33 out of these 36 patients (91.7%) were objectively cured (p = 0.98). No significant deterioration of subjective and objective cure rates was observed over time (p for trend 0.50 and 0.48). Fifteen of the 36 patients (41.6%) at the 20-year follow-up reported the onset of de novo overactive bladder (OAB) (p = 0.004). No significant vaginal bladder or urethral erosion or de novo dyspareunia was recorded and no patient required tape release or resection during this period. The cause of death of seven out of ten women who died in the last year of the follow-up period was coronavirus disease 19 (COVID 19). Conclusions The 20-year results of this study showed that TVT is a highly effective and safe option for the treatment of SUI. The impact of COVID 19 on the mortality rate of elderly women has drastically reduced the number of eligible patients for future evaluations in our region.

Although it is known that hysterectomy (HY) alone cannot resolve apical prolapse, vaginal hysterectomy (VH) remains the most common surgical procedure for this issue. In recent years, various procedures for uterine conservation have been proposed to avoid the surgical risks of HY. Furthermore, most women with symptomatic pelvic organ prolapse (POP) prefer uterine conservation in the absence of considerable benefit in uterine removal. In 2017, we proposed a new technique for hysteropexy and anterior vaginal native tissue repair (NTR) in women with cystocele and apical prolapse. The objective of this study is to assess the efficacy and safety of this new procedure after at least 5 years of follow-up. We included only patients with stage II or greater prolapse of the anterior vaginal wall and a concomitant stage II uterine prolapse in accordance with Pelvic Organ Prolapse Quantification (POP-Q) system. A Patient Global Impression of Improvement (PGI-I) score ≤ 2 in addition with the absence of POP symptoms was defined as subjective success. A descensus with a maximum point of less than −1 in any compartment was considered objective cure. A total of 102 patients who fulfilled the inclusion criteria were enrolled. At 60 months follow-up, 90 out of 102 patients (88%) were subjectively cured, whereas 88 out of the 102 (86%) patients were objectively cured. Subjective and objective cure rates persisted during the entire study period. Uni- and multivariate analysis of possible predictive factors associated with recurrence of prolapse showed that only a preoperative point C > 0 cm and BMI ≥ 25 kg/m2 were risk factors for failure. In conclusion, our study showed that hysteropexy with anterior vaginal native tissue repair may be an effective and safe option for the treatment of anterior vaginal prolapse and concomitant stage II uterine prolapse by at least 5 years of follow-up.

OBJECTIVE To compare outcomes after hysterectomy and hysterectomy plus sentinel node mapping (SNM) in endometrial cancer (EC) patients. MATERIALS AND METHODS This is a retrospective study, collecting data of EC patients treated between 2006 and 2016 in nine referral centers. RESULTS The study population included 398 (69.5%) and 174 (30.5%) patients having hysterectomy and hysterectomy plus SNM. As the results of the adoption of a propensity-score matched analysis, we selected two homogeneous cohort of patients (150 having hysterectomy only vs. 150 having hysterectomy plus SNM). The SNM group had a longer operative time, but did not correlate with length of hospital stay and estimated blood loss. Overall severe complication rates were similar between groups (0.7% in the hysterectomy group vs. 1.3% in the hysterectomy plus SNM group; p = 0.561). No lymphatic-specific complication occurred. Overall, 12.6% of patients having SNM were diagnosed with disease harboring in their lymph nodes. Adjuvant therapy administration rate was similar between groups. Considering patients having SNM, 4% of patients received adjuvant therapy on the basis of nodal status alone; all the other patients received adjuvant therapy also on the basis of uterine risk factors. Five-year disease-free (p = 0.720) and overall (p = 0.632) survival was not influenced by surgical approach. CONCLUSIONS Hysterectomy (with or without SNM) is a safe and effective method for managing EC patients. Potentially, these data support the omission of side specific lymphadenectomy in case of unsuccessful mapping. Further evidence is warranted in to confirm the role SNM in the era of molecular/genomic profiling.

STUDY OBJECTIVE To investigate the postoperative morbidity of laparoscopic hysterectomy (LH) for endometriosis/adenomyosis in terms of operative outcomes and complications. DESIGN Retrospective multicentric cohort study. SETTING Eight European minimally invasive referral centers. PATIENTS Data from 995 patients with pathologically confirmed endometriosis and/or adenomyosis who underwent LH without concomitant urological and/or gastroenterological procedures from January 2010 to December 2020. INTERVENTIONS Total laparoscopic hysterectomy. MEASUREMENTS AND MAIN RESULTS Demographic patients' characteristics, surgical outcomes, and intraoperative and postoperative complications were evaluated. We considered major postoperative surgical-related complications any grade 2 or more events (Clavien-Dindo score) that occurred within 30 days from surgery. Univariate analysis and multivariable models fit with logistic regression were used to estimate the adjusted odds ratio (OR) and corresponding 95% CI for major complications. Median age at surgery was 44 years (28-54) and about half of them (505, 50.7%) were on medical treatment (estro-progestins, progestin or GnRh-analogues) at the time of surgery. In association with LH, posterior adhesiolysis was performed in 387 (38,9%) cases and deep nodule resection in 302 (30,0%). Intraoperative complications occurred in 3% of the patients and major postoperative complications were registered in 93 (9.3%). The multivariable analysis showed an inverse correlation between the occurrence of Clavien-Dindo >2 complications and age (OR 0.94, 95%CI 0.90-0.99), while previous surgery for endometriosis (OR 1.62, 95%CI 1.01-2.60) and intraoperative complications (OR 6.49, 95%CI 2.65-16.87) were found as predictors of major events. Medical treatment at the time of surgery has emerged as a protective factor (OR 0.50, 95%CI 0.31-0.81). CONCLUSION LH for endometriosis/adenomyosis is associated with non-negligible morbidity. Knowing the factors associated with higher risks of complications might be used for risk stratification and could help clinicians during preoperative counseling. The administration of estro-progestin or progesterone preoperatively might reduce the risks of postoperative complications following surgery.

OBJECTIVE To investigate factors predicting the risk of developing 90-day postoperative complications and lymphatic-specific morbidity in patients undergoing surgical staging for high-risk endometrial cancer. METHODS This is a multi-institutional retrospective cohort study. Patients affected by apparent early-stage high-risk endometrial cancer (endometrioid FIGO grade 3 with deep myometrial invasion and non-endometrioid endometrial cancer) undergoing surgical staging between 2007 and 2019. Complications were graded according to the Clavien-Dindo classification system. Martin criteria were applied to improve quality of complications reporting. RESULTS Charts of 279 patients were evaluated. Lymphadenectomy, sentinel node mapping (SNM), and SNM followed by back-up lymphadenectomy were performed in 83 (29.7%), 50 (17.9%), and 146 (52.4%) patients, respectively. The former group of patients included 13 patients who had lymphadenectomy after the failure of the SNM technique. Thirteen (4.6%) patients developed severe postoperative events (grade 3 or worse). At multivariate analysis, body mass index (OR: 1.08 (95%CI: 1.01, 1.17)) and open abdominal surgery (OR: 2.27 (95%CI: 1.02, 5.32)) were the two independent factors predictive of surgery-related morbidity. Seven severe lymphatic complications occurred. The adoption of laparoscopic approach (p��

Background: The primary objective of this study was to assess the associations of computed tomography (CT)-based whole-body composition values with overall survival (OS) and progression-free survival (PFS) in epithelial ovarian cancer (EOC) patients. The secondary objective was the association of body composition with chemotherapy-related toxicity. Methods: Thirty-four patients (median age 64.9 years; interquartile range 55.4–75.4) with EOC and thorax and abdomen CT scans were included. Clinical data recorded: age; weight; height; stage; chemotherapy-related toxicity; and date of last contact, progression and death. Automatic extraction of body composition values was performed by dedicated software. Sarcopenia was defined according to predefined cutoffs. Statistical analysis included univariate tests to investigate associations of sarcopenia and body composition with chemotoxicity. Association of body composition parameters and OS/PFS was evaluated by log-rank test and Cox proportional hazard model. Multivariate models were adjusted for FIGO stage and/or age at diagnosis. Results: We found significant associations of skeletal muscle volume with OS (p = 0.04) and PFS (p = 0.04); intramuscular fat volume with PFS (p = 0.03); and visceral adipose tissue, epicardial and paracardial fat with PFS (p = 0.04, 0.01 and 0.02, respectively). We found no significant associations between body composition parameters and chemotherapy-related toxicity. Conclusions: In this exploratory study, we found significant associations of whole-body composition parameters with OS and PFS. These results open a window to the possibility to perform body composition profiling without approximate estimations.

Functional magnetic stimulation (FMS) is a new technique for the conservative treatment of Urinary incontinence (UI), based on magnetic induction. It induces controlled depolarization of the nerves, resulting in pelvic muscle contraction and sacral S2-S4 roots neuromodulation. The aim of this study was to assess the efficacy of the new 3 Tesla FMS chair, both in patients with pure stress urinary incontinence (SUI) and in women with pure overactive bladder (OAB) symptoms. A prospective observational study was conducted in our urogynaecologic unit. All the patients involved were consecutive women with pure SUI or pure OAB symptoms treated by a 3 Tesla electromagnetic chair. The primary outcome was a subjective outcome evaluation by the PGI-I Scale and a patient-satisfaction scale. The secondary outcome was the change score of the UDI-6, IIQ-7, ICIQ-SF and OAB-q SF questionnaires from baseline to final visit. At 2 months follow-up, 28 out of 60 patients (47%) with SUI symptoms and 20 out of 40 patients (50%) with OAB symptoms declared themselves cured. Considering cured and improved patients, the subjective cure rates were 68.3% (41/60) and 70% (28/40) for patients with SUI and OAB symptoms, respectively. The results of this study showed that the 3 Tesla electromagnetic chair may be an effective option for the treatment of UI.

OBJECTIVE Sentinel lymph node mapping (SNM) has gained popularity in managing apparent early-stage endometrial cancer (EC). Here, we evaluated the long-term survival of three different approaches of nodal assessment. METHODS This is a multi-institutional retrospective study evaluating long-term outcomes of EC patients having nodal assessment between 01/01/2006 and 12/31/2016. In order to reduce possible confounding factors, we applied a propensity-matched algorithm. RESULTS Overall, 940 patients meeting inclusion criteria were included in the study, of which 174 (18.5%), 187 (19.9%), and 579 (61.6%) underwent SNM, SNM followed by backup lymphadenectomy (LND) and LND alone, respectively. Applying a propensity score matching algorithm (1:1:2) we selected 500 patients, including 125 SNM, 125 SNM/backup LND, and 250 LND. Baseline characteristics of the study population were similar between groups. The prevalence of nodal disease was 14%, 16%, and 12% in patients having SNM, SNM/backup LND and LND, respectively. Overall, 19 (7.6%) patients were diagnosed with low volume nodal disease. The survival analysis comparing the three techniques did not show statistical differences in terms of disease-free (p = 0.750) and overall survival (p = 0.899). Similarly, the type of nodal assessment did not impact survival outcomes after stratification based on uterine risk factors. CONCLUSION Our study highlighted that SNM provides similar long-term oncologic outcomes than LND.

OBJECTIVES A higher risk for adverse pregnancy outcome is associated with SARS-CoV-2 infection, which could be partially explained by an altered placental function. Since histopathology is often unspecific, we aimed to assess placental weight, birthweight/placental-weight (b/p) ratio and the metabolic scaling exponent ��, an indicator of a normal fetal-placental growth, in order to analyze the placental function. METHODS We included 153 singleton pregnancies with SARS-CoV-2 positive PCR in our study, who delivered at three referring hospitals in Switzerland. Placental weight and b/p ratio were compared to published reference charts. Logistic regression analysis investigated the role of time of infection and other confounding factors on placental weight. The scaling exponent �� was compared to the reference value of ��. RESULTS Placental weight was inferior or equal to the 10th centile in 42.5%(65/153) and to the 3rd centile in 19%(29/153) of the cases. The risk of low placental weight was not influenced by the trimester of infection. B/p ratio was >50th centile in 80.4%(123/153) of the cases. Incidence of fetal growth restriction, preeclampsia and gestational diabetes was 11.8%(18/153), 3.3%(5/153) and 19.6%(30/153). Linear regression modelling revealed a pathologic metabolic scaling exponent �� of 0.871��0.064 (R2=0.56). CONCLUSION SARS-CoV-2 during pregnancy was associated with a higher incidence of low placental weight, an increased b/p ratio and an abnormal scaling exponent �� in our cohort. This could be particularly relevant for the yet controversial issue of increased stillbirth rate in SARS-CoV-2 infection during pregnancy. In this regard, intensified fetal surveillance should be mandatory in these pregnancies.

PURPOSE We aimed to assess the impact of low-volume metastasis (micrometastasis and isolated tumor cells) on disease-free survival (DFS) of women with early-stage cervical cancer. METHODS Women with clinically suspected stage 1A-IB2 (FIGO 2018 classification) disease who underwent retroperitoneal nodal staging between October 2010 and April 2018, were retrospectively analyzed. The group of women who had undergone lymphadenectomy and standard node pathologic analysis (H&E group), were compared to the group undergoing sentinel node mapping (SLN) and ultrastaging with or without lymphadenectomy (ultrastaging group). At a median follow-up of 45 months, the DFS curves were analyzed. RESULTS Overall, 573 patients were revised (272 in the H&E group and 302 in the ultrastaging group). Eighty-five patients presented lymph node metastasis (32 in H&E, 53 in ultrastaging). Ultrastaging protocol increased the rate of low-volume metastasis by 5.6%. Twenty patients showed exclusive micrometastasis or ITC's. Seventy-three recurrences occurred (35 in H&E, 38 in ultrastaging). Only 1 out of 53 patients in the ultrastaging group (1.9%) presented with micrometastasis recurred. The 3-year disease-free survival was 89% for the H&E group, and 88% for the ultrastaging group, respectively (p = 0.175). CONCLUSION Ultrastaging analysis allowed increasing the detection of low volume metastasis in women with early-stage cervical cancer. However, the type of nodal staging did not have an impact on patients' 3-year disease-free survival.

Although unilateral oophorectomies are performed more often than bilateral ones in women of reproductive age, their clinical consequences have been less intensively investigated. Experimental models in animals have shown that compensatory mechanisms occur after a unilateral oophorectomy (UO). This review aims to summarize the available evidence on the biological effects of unilateral oophorectomy on women. Evaluated outcomes include age at onset of menopause, risk of cardiovascular and neurological disease, risk of mortality and fertility outcome after spontaneous conception or in vitro fertilization (IVF). Results were compared with findings reported after bilateral oophorectomy and/or ovarian excision and/or women with intact ovaries. An electronic database search was performed using PubMed and Scopus, followed by a manual search to identify controlled studies that compared women after UO with women with two intact ovaries. In particular, a systematic review of fertility outcomes after IVF was performed, and the data were summarized in a table. Women who underwent UO had a similar age at menopause and similar clinical pregnancy rate compared to women with two ovaries. However, decreased ovarian reserve affecting the quantity but not the quality of the ovarian pool after IVF was observed in the UO group. Furthermore, an increased risk of neurological disease and even an increased risk of mortality was observed in women with single ovary. These data need to be confirmed by further studies, and a plausible mechanism of action must be identified. At present, patients who undergo UO can be reassured with regard to their reproductive potential and their age at onset of menopause.Obwohl einseitige Ovarektomien häufiger als bilaterale Eierstockentfernungen bei Frauen im reproduktionsfähigen Alter durchgeführt werden, hat man den klinischen Folgen von einseitigen Ovarektomien weniger Aufmerksamkeit gewidmet. Experimentelle Tiermodelle zeigen, dass Kompensationsmechanismen nach einseitigen Ovarektomien stattfinden. Ziel dieser Übersichtsarbeit war es, die existierenden Forschungsergebnisse zu den biologischen Auswirkungen von einseitigen Ovarektomien zusammenzufassen. Zu den untersuchten Aspekten zählten Alter bei Eintritt der Wechseljahre, Risiko für Herz-Kreislauf-Erkrankungen und neurologische Erkrankungen, Mortalitätsrisiko und Fertilitätsergebnis nach spontaner Empfängnis oder In-vitro-Fertilisation (IVF). Diese Ergebnisse wurden mit den Ergebnissen nach bilateraler Ovarektomie und/oder ovarieller Exzision bzw. von Frauen mit intakten Eierstöcken verglichen. Es wurde zunächst eine elektronische Datenbanksuche mithilfe von PubMed und Scopus durchgeführt. Danach wurde eine manuelle Suche durchgeführt, um kontrollierte Studien auszumachen, die Frauen nach einseitiger Ovarektomie mit Frauen mit 2 intakten Eierstöcken verglichen. Es wurde eine systematische Überprüfung der Fertilitätsergebnisse nach IVF durchgeführt, und die Daten wurden in einer Tabelle zusammengefasst. Bei Frauen, die sich einer einseitigen Ovarektomie unterzogen hatten, waren das Alter bei Eintritt der Wechseljahre sowie die klinischen Schwangerschaftsraten ähnlich wie bei Frauen mit 2 Eierstöcken. Es wurde zwar eine verminderte ovarielle Reserve bei Frauen nach einer einseitigen Ovarektomie festgestellt; diese wirkte sich aber auf die Quantität, nicht auf die Qualität des ovariellen Pools nach IVF aus. Es wurde ferner ein erhöhtes Risiko für neurologische Erkrankungen und sogar ein erhöhtes Mortalitätsrisiko bei Frauen mit nur einem Eierstock beobachtet. Diese Daten müssen in weiteren Studien bestätigt werden, und ein plausibler Wirkungsmechanismus dafür muss noch identifiziert werden. Nach aktuellem Wissensstand können Patientinnen, die sich einer einseitigen Ovarektomie unterziehen, hinsichtlich ihres reproduktiven Potenzials und ihres Alters bei Eintritt der Wechseljahre beruhigt sein.

Surgical staging in endometrial cancer has evolved and sentinel lymph node (SLN) mapping has replaced a full pelvic and paraaortic lymphadenectomy in several cases. An intraoperative evaluation of SLN might identify patients who could benefit the most from a full lymphadenectomy. The aim of this study is to evaluate the clinical relevance of frozen section of SLN. A retrospective analysis in patients with endometrial cancer who underwent SLN mapping with intraoperative evaluation at frozen section between February 2016 and September 2019 was performed. In case of metastatic involvement, a full lymphadenectomy was performed. Fifty-eight patients met the inclusion criteria. Clinical–pathologic characteristics of the patients and surgical data were analyzed. Overall, bilateral and unilateral detection rates were 100% (58/58), 89.7% (52/58), and 10.3% (6/58), respectively. Eight patients had a stage IIIC disease at permanent section. Frozen section detected SLN metastases in four of eight patients. Of these, two were micrometastases and two were macrometastases. At frozen section of the SLNs, no macrometastases were misdiagnosed. Sensitivity, specificity, accuracy, positive predictive value and negative predictive value of frozen section in detecting metastases was 50%, 100%, 93%, 100% and 92.6%, respectively. The intraoperative evaluation of SLN in endometrial cancer accurately identifies patients with macrometastases. This is the cohort that might benefit the most of a full lymphadenectomy for a higher risk of additional lymph node metastases.

To evaluate the difference in oncologic outcome between vulvar cancer patients with uni- and bilateral inguino-femoral lymph nodal involvement and to identify factors affecting their oncologic outcome Patients who underwent inguino-femoral lymphadenectomy for vulvar cancer were classified into three groups according to their lymph nodal status at the histology analysis (negative, positive one side, positive bilaterally). PFS and OS survival were calculated using the Kaplan–Meier method. Univariate and multivariate analyses were performed to analyze factors predicting overall survival and progression-free survival. Multivariable models were used for variables reporting a p value ≤ 0.1 at the univariate analysis. p values ≤ 0.05 were considered statistically significant. One hundred and forty-six patients were considered for the analysis. Patients with bilaterally negative lymph nodes had significantly longer PFS and OS as compared to patients with unilateral and bilateral involvement. Patients with unilateral lymph nodal involvement had better PFS than patients with bilateral lymph nodal involvement. Among these patients, the difference in the OS approached but did not reach statistical significance. At the multivariate analysis, the tumor size affected PFS and lymph nodal involvement affected OS. Vulvar cancer patients with bilateral positive lymph nodes have worse oncologic outcome as compared to patients with unilateral lymph nodal involvement; similarly, patients with unilateral lymph nodal involvement have worse oncological outcome as compared to patients with bilateral negative lymph nodes. Furthermore, tumor size and lymph nodal status are independent factors predicting recurrence rate and overall survival, respectively.

The chapter argues theoretically that economic recessions spur tax introductions, and investigates this claim empirically. It finds that recessions have indeed sped up the adoption of some taxes in a global sample of countries as the ‘recessionist’ hypothesis would suggest. This effect was particularly pronounced for inheritance taxes and social security contributions. Yet it also finds that recessions slowed down the introduction of other taxes, most notably personal income and value added taxes. The chapter identifies a change of the relationship between recessions and tax introductions in the 1930s, arguably reflecting the emergence of new ideas in economics and policy making related to the Great Depression. It concludes with a case study of inheritance tax introductions during the Long Depression of the nineteenth century. The study shows how the interaction between recessions and tax introductions unfolded in Great Britain and elsewhere.

Recurrent stress urinary incontinence (rSUI) represents a major challenge for most clinicians as there is little evidence in the literature on the best option after sling failure. The objective of this study is to summarise the findings on the use of urethral bulking agents (UBAs) in the management of rSUI after the failure of a mid-urethral sling (MUSs). We performed a systematic review and meta-analysis, according to PRISMA 2020 guidelines, and selected eleven publications for inclusion in the analysis. We found that the overall cure and improvement rate ranged from 64% to 85% in the included studies, with a pooled value of 75%, compared with pooled failure and re-operation rates of 32% (95% CI: 22%-43%) and 25% (95% CI: 17%-34%), respectively. The I-2 test indicated significant statistical heterogeneity among the studies in relation to all the outcome measures; however, no risk of publication bias was found. To explore this heterogeneity in more depth, we performed a sub-group analysis of the two most commonly used bulking agents (Bulkamid and Macroplastique). The pooled values of the cure and improvement rate were 84% (95% CI: 77.0%-90.0%) and 80% (95% CI: 74.0%-85.0%) for Macroplastique and Bulkamid, respectively. We did not find significant heterogeneity or significant differences in the outcome measures in either group.For the first time in literature, our study provides an insight into the use of UBAs after failed MUSs. Although the results seem very promising, future studies with shared protocols are needed in order to recommend the use of UBAs in the treatment of recurrent cases.

Contains fulltext : 283074.pdf (Publisher’s version ) (Open Access) OBJECTIVE: The aim of this study was to assess the SLN detection rate in presumed early stage, low- and intermediate-risk endometrial cancers, the incidence of SLN metastases, and the negative predictive value of SLN mapping performed with indocyanine green (ICG). METHODS: A systematic review with meta-analyses was conducted. Study inclusion criteria were A) low- and intermediate-risk endometrial cancer, B) the use of ICG per cervical injection; C) a minimum of twenty included patients per study. To assess the negative predictive value of SLN mapping, D) a subsequent lymphadenectomy was an additional inclusion criterion. RESULTS: Fourteen studies were selected, involving 2,117 patients. The overall and bilateral SLN detection rates were 95.6% (95% confidence interval [CI]=92.4%-97.9%) and 76.5% (95% CI=68.1%-84.0%), respectively. The incidence of SLN metastases was 9.6% (95% CI=5.1%-15.2%) in patients with grade 1-2 endometrial cancer and 11.8% (95% CI=8.1%-16.1%) in patients with grade 1-3 endometrial cancer. The negative predictive value of SLN mapping was 100% (95% CI=98.8%-100%) in studies that included grade 1-2 endometrial cancer and 99.2% (95% CI=97.9%-99.9%) in studies that also included grade 3. CONCLUSION: SLN mapping with ICG is feasible with a high detection rate and negative predictive value in low- and intermediate-risk endometrial cancers. Given the incidence of SLN metastases is approximately 10% in those patients, SLN mapping may lead to stage shifting with potential therapeutic consequences. Given the high negative predictive value with SLN mapping, routine lymphadenectomy should be omitted in low- and intermediate-risk endometrial cancer.

Sentinel lymph nodes are widely accepted in the treatment of endometrial carcinoma. Whereas surgical aspects are well studied, the pathological work-up in terms of grossing, frozen section, and the so-called ultra-staging is still a matter of debate. This results in conflicting national or center-based recommendations. In a series of consecutive 833 sentinel lymph nodes from 206 patients in endometrial carcinomas, we compared three different grossing techniques and the use of frozen section in terms of anatomy, detection rates, and survival. In total, 42 macro-metastases, 6 micro-metastases, and 25 nodes with isolated tumor cells were found. Lymph nodes affected at least with micro-metastasis were about 0.5cm enlarged. Detection rates in lamellation technique increased with a step of 5.9% to 8.3% in comparison to bi-valved or complete embedding. The lamellation technique presented with a slight beneficial prognosis in pN0 subgroup (OS, p=0.05), which besides size effects might be attributed to trimming loss. In frozen section, this effect was less pronounced than expected (OS, p=0.56). Ultra-staging only revealed additional micro-metastases and isolated tumor cells. Exclusively, macro-metastases showed poor survival (p

BACKGROUND SARS-CoV-2 positive pregnant women are at higher risk of adverse outcomes, but little evidence is available on how variants impact that risk. We aim to evaluate maternal and perinatal outcomes among unvaccinated pregnant women that tested positive for SARS-CoV-2, stratified by pre-Delta, Delta, and Omicron periods. METHODS This prospective study enrolled women from March 2020 to September 2022. Exposure to the different SARS-CoV-2 variants was defined by their periods of predominance. The primary outcome was severe maternal adverse outcome defined as either intensive care unit admission, acute respiratory distress syndrome, advanced oxygen supplementation, or maternal death. The secondary outcomes were preterm birth and other perinatal outcomes. FINDINGS Overall, 1402, 262, and 391 SARS-CoV-2 positive pregnant women were enrolled during the pre-Delta, Delta, and Omicron periods respectively. Severe maternal adverse outcome was reported in 3.4% (n = 947/1402; 95% confidence intervals (95%CI) 2.5-4.5), 6.5% (n = 7/262; 95%CI 3.8-10.2), and 1.0% (n = 4/391; 95%CI 0.3-2.6) of women during the pre-Delta, Delta, and Omicron periods. The risk of severe maternal adverse outcome was higher during the Delta vs pre-Delta period (adjusted risk ratio (aRR) = 1.8; 95%CI 1.1-3.2) and lower during the Omicron vs pre-Delta period (aRR = 0.3; 95%CI, 0.1-0.8). The risks of hospitalization for COVID-19 were 12.6% (n = 176/1402; 95%CI 10.9-14.4), 17.2% (n = 45/262; 95%CI 12.8-22.3), and 12.5% (n = 49/391; 95%CI 9.4-16.2), during the pre-Delta, Delta, and Omicron period, respectively. Pregnancy complications occurred after SARS-CoV-2 exposure in 30.0% (n = 363/1212; 95%CI 27.4-32.6), 35.2% (n = 83/236; 95%CI 29.1-41.6), and 30.3% (n = 105/347; 95%CI 25.5-35.4) of patients during the pre-Delta, Delta, and Omicron periods, respectively. Stillbirths were reported in 0.5% (n = 6/1159; 95%CI 0.2-1.1), 2.8% (n = 6/210; 95%CI 1.0-6.0), and 0.9% (n = 2/213; 95%CI 0.1-3.4) or patients during the pre-Delta, Delta, and Omicron periods respectively. INTERPRETATION The Delta period was associated with a higher risk of severe maternal adverse outcome and the Omicron period with a lower risk of severe adverse outcome compared to pre-Delta era. The reported risk of hospitalization was high during the Omicron period and should not be trivialized. FUNDING Swiss Federal Office of Public Health, Fondation CHUV.

The SMARCA subgroup of genes belongs to the SWI1/SNF1 family, responsible for chromatin remodeling and repair within the nucleosome. The SMARCA4 gene is located on chromosome 19p13 and encodes the BRG1 (BRAhMA) protein. We report the cytological and histological findings in one case of large cell SMARCA4 deficient ovarian carcinoma with positive peritoneal washing in a 69-year-old woman. The neoplastic cells were present as singly lying or perivascular clusters and showed medium or large size, round to oval hyperchromatic nuclei, and scarce to moderate cytoplasms. Molecular pathology investigations performed on the ovarian surgical sample found two previously undescribed mutations in the SMARCA4 gene and additional mutations in the CTNNB1 (Beta Catenin gene) and in PIK3CA. To our knowledge, this case probably represents the third cytologic report of this variant of ovarian carcinoma and the first one with molecular pathologic study.

Introduction/Background* Sentinel node mapping (SNM) has replaced lymphadenectomy for staging surgery in apparent early-stage endometrial cancer (EC). Here, we evaluate the long-term survival of three different approaches of nodal assessment in low, intermediate, and high-risk EC. Methodology This is a multi-institutional retrospective study evaluating long-term outcomes (at least 3 years of follow-up) of EC patients having nodal assessment between 2006 and 2016. In order to reduce possible confounding factors, we applied a propensity-matched algorithm. Result(s)* Charts of 940 patients were evaluated: 174 (18.5%), 187 (19.9%), and 579 (61.6%) having SNM, SNM followed by backup lymphadenectomy and lymphadenectomy, respectively. Applying a propensity score matching algorithm (1:1:2) we selected 500 patients: 125 SNM vs. 125 SNM plus backup lymphadenectomy vs. 250 lymphadenectomy. Baseline characteristics of the study population were similar between groups. The prevalence of nodal disease was 14%, 16%, and 12% in patients having SNM, SNM followed by backup lymphadenectomy and lymphadenectomy, respectively. Overall, 19 (7.6%) patients were diagnosed with low volume nodal disease (7 and 12 patients with micrometastasis and isolated tumor cells). The mean (SD) follow-up time was 62 (±11) months. The survival analysis comparing the three techniques did not show statistical differences in terms of disease-free (p=0.750) and overall survival (p=0.899). Similarly, the type of nodal assessment did not impact survival outcomes after stratification on the basis of uterine risk factors. Conclusion* Our study highlighted that SNM provides similar long-term oncologic outcomes than lymphadenectomy. Further evidence is warranted to assess the prognostic value of low-volume disease detected by ultrastaging and the role of molecular/genomic profiling.

Introduction Preliminary clinical evidence suggests a detrimental effect of pathogenic variants of BRCA1 and 2 genes on fertility outcome. This meta-analysis evaluates whether women carrying BRCA mutations (BRCAm) have decreased ovarian reserve, in terms of Anti-Muellerian Hormone (AMH), compared to women without BRCAm (wild-type). Material and methods Systematic searches of PubMed, Medline, Scopus, Embase, Science Direct and the Cochrane Library from inception until July 2020 were conducted. All studies comparing AMH level in fertile age women, with and without BRCA pathogenic variants were considered. Sub-analyses were performed according to age, presence of breast cancer, and type of mutation. Results Among 64 studies, 10 series were included. For the entire cohort, a trend of reduced AMH level were found between BRCAm carriers and women without pathogenic variants. BRCAm carriers aged 41-years or younger had lower AMH levels compared to 41-years or younger wild type women (OR: 0.73 [95%CI-1.12;-0.35]; p = 0.0002). This finding was confirmed for BRCA1m carriers (OR: 1 [95%CI-1.96;-0.05]; p = 0.004) whereas no difference was observed between BRCA2m carriers and wild type women. The same analysis on breast cancer patients with and without BRCAm achieved the same results. Conclusion Young BRCA1m carriers seem to have lower AMH level compared with wild type women and therefore a potential decreased ovarian reserve., Graphical abstract Image 1, Highlights • BRCAm carriers have similar AMH levels to wild-type women. • In women under 42 years old, AMH level is statistically lower in BRCA1m. • Fertility preservation counselling should be offered once BRCA pathogenic variant is diagnosed.

Pregnant women may be at higher risk of severe complications associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may lead to obstetrical complications. We performed a case control study comparing pregnant women with severe coronavirus disease 19 (cases) to pregnant women with a milder form (controls) enrolled in the COVI-Preg international registry cohort between March 24 and July 26, 2020. Risk factors for severity, obstetrical and immediate neonatal outcomes were assessed. A total of 926 pregnant women with a positive test for SARS-CoV-2 were included, among which 92 (9.9%) presented with severe COVID-19 disease. Risk factors for severe maternal outcomes were pulmonary comorbidities [aOR 4.3, 95% CI 1.9-9.5], hypertensive disorders [aOR 2.7, 95% CI 1.0-7.0] and diabetes [aOR2.2, 95% CI 1.1-4.5]. Pregnant women with severe maternal outcomes were at higher risk of caesarean section [70.7% (n = 53/75)], preterm delivery [62.7% (n = 32/51)] and newborns requiring admission to the neonatal intensive care unit [41.3% (n = 31/75)]. In this study, several risk factors for developing severe complications of SARS-CoV-2 infection among pregnant women were identified including pulmonary comorbidities, hypertensive disorders and diabetes. Obstetrical and neonatal outcomes appear to be influenced by the severity of maternal disease. ispartof: SCIENTIFIC REPORTS vol:11 issue:1 ispartof: location:England status: published

Introduction and hypothesis: Several studies have shown that immediate catheter removal following pelvic surgery is associated with several advantages. The aim of this case–control study is to compare immediate versus delayed catheter removal following mid-urethral sling surgery, to determine if indwelling catheterisation is necessary after this procedure. The secondary outcomes were subjective and objective cure rate after at least a 1-year follow-up. Methods: Cases were defined as all the women who underwent a TVT Abbrevo for urodynamically proven stress incontinence. In every case the Foley catheter was removed by the surgeon at the end of the procedure. A voided volume >200ml with a post-void residual of

We aimed to evaluate weather survival is impaired in stage IIIC endometrial cancer patients treated with minimally invasive surgery as compared to laparotomy. We analyzed surgical data and oncologic outcome of histologically proven stage IIIC endometrial cancer patients who were treated at our institution via laparotomy or via laparoscopic surgery. All the patients underwent a systematic pelvic and para-aortic lymphadenectomy and a complete tumor resection. Perioperative morbidity and overall survival of the patients subjected to the two surgical approaches were compared. Sixty-six patients with stage IIIC endometrial cancer were identified. Of these, 15 patients were operated via laparotomy and 51 via laparoscopy. The two groups were similar with regards to median age at diagnosis, BMI, histotype, number of affected lymph nodes, and median maximal diameter of the affected lymph nodes. Patients undergoing laparoscopic surgery had fewer perioperative complications, a smaller estimated blood loss, and were subjected less frequently to transfusions. Overall survival at 60 months of follow-up did not differ between the two groups. At uni- and multivariate analysis, surgical approach did not affect survival. Only age was a variable associated with overall survival. Minimally invasive surgery has better perioperative outcomes and does not impair survival in stage IIIC endometrial cancer patients. Age at diagnosis is the only factor independently affecting survival.

The tension-free vaginal tape ABBREVO (TVT-A) is a new surgical procedure for the treatment of female stress urinary incontinence (SUI). However, data reporting medium- and long-term outcomes are lacking. The aim of the study was to assess the efficacy and safety of TVT-A in patients with at least a 3-year follow-up. All consecutive women who complained of pure SUI symptoms with urodynamically proven SUI undergoing a TVT-A procedure were prospectively enrolled. Data regarding subjective outcomes (International Consultation on Incontinence Questionnaire-Short Form, Patient Global Impression of Improvement and patient satisfaction scores), objective cure (stress test) rates and adverse events were collected during follow-up. Univariate analysis was performed to investigate outcomes. A total of 41 women underwent TVT-A implantation. At 3-year follow-up, 40 women (97.5%) were available for the evaluation. We did not find any significant change in surgical outcomes during this time. At 3 years after surgery, 36 of 40 (90%) patients were subjectively cured (p for trend 0.18) and 37 out of 40 (92.5%) patients were objectively cured (p for trend 0.22). The univariate analysis did not find any risk factor statistically associated with the recurrence of SUI. A significant trend of de novo overactive bladder (OAB) occurrence was registered at the 3-year follow-up (p for trend = 0.03). No serious late complications or groin-thigh pain were reported. TVT-A implantation is a highly effective option for the treatment of women with pure SUI.

The first laparoscopic procedure was performed by 1901 by Georg Kelling in dogs while the first laparoscopic procedure in humans was performed by Hans Chrisitan Jacobaeus in 1910. Minimally invasive surgery offers multiple advantages over conventional laparotomy and is associated with reduced estimated blood loss, a lower incidence of complications and a shorter hospital stay and recovery. Over a century later, the vast majority of surgical procedures in gynecology are performed via minimal invasive technique. These include laparoscopy, minilaparoscopy, robotic surgery, laparoendoscopic single site surgery (LESS) and natural orifices transluminal endoscopic surgery. In this chapter we review these surgical techniques, analyze the main differences among these techniques and comment on their advantages and disadvantages.